A systematic review of clinical trials of treatment regimens in HER2-amplified metastatic colorectal cancer.

INTRODUCTION: Targeting HER2 has led to a revolution in therapy for cancers such as breast and gastric cancer, HER2 amplification is rarer (just 2-6%) in colorectal cancer (CRC) and efforts to target this receptor have lagged. Despite recent FDA approval for the first directed therapy combination for HER2 amplified metastatic CRC, the EMA has not yet authorized any such treatment and this represents a persistent unmet need in Europe and beyond. Here, we review data from trials targeting HER2 amplification, the latest target for CRC therapy. AREAS COVERED: PubMed, Cochrane Library, EMBASE, and clinicaltrials.gov were reviewed systematically for possible manuscripts from inception to 1 July 2022. Results: A total of seven studies comprised of 284 locally advanced/mCRC patients receiving HER2 targeting agents were included in this systematic review. Most of the studies (n = 5) were non-randomized phase 2 trials, one phase 2/3 randomized controlled trial, and one phase 2a multiple-basket study. The outcomes consisted in the analysis of HER2 targeting agents and ORR, PFS, OS benefit, and toxicities of the therapy. EXPERT OPINION: Anti-HER2 therapy exhibits a favorable toxicity profile compared with other targeted approaches; however, there is work to be done on optimizing patient selection and understanding resistance mechanisms.